Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Inhibitors of pi3k p-delta 110 for use in delivery of viruses in the treatment of cancer

An inhibitor, virus technology, applied in the field of PI3K P-δ110 inhibitors used to deliver viruses in cancer treatment, can solve problems such as lack of immune activity

Pending Publication Date: 2019-01-15
QUEEN MARY UNIV OF LONDON
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, these experimental models are not immunocompetent, and it is clear that host immunity is a major barrier to the successful implementation of modified viruses for cancer therapy

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Inhibitors of pi3k p-delta 110 for use in delivery of viruses in the treatment of cancer
  • Inhibitors of pi3k p-delta 110 for use in delivery of viruses in the treatment of cancer
  • Inhibitors of pi3k p-delta 110 for use in delivery of viruses in the treatment of cancer

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Example 1: Infection of Tumor Cells by Modified Viruses in Nude and Immunocompetent Mouse Models

[0068] figure 1 A shows that at 3 hours, p110δ RNA was significantly more (Pfigure 1 B shows that this upregulation of p110δ RNA is translated into protein expression in immunocompetent mouse macrophages treated with virus compared with mock treatment. figure 1 C shows that inhibition of p110δ by IC87114 (a selective inhibitor) significantly reduces the adsorption of VVL15 to macrophages.

[0069] Although IC87114 is considered to be very specific, it must block other kinases (Camps et al., Nat Med, 2005.11(9):p.936-43). Therefore, confirmation is needed to confirm that the observed decrease in VVL15 adsorption is in fact due to IC87114 blocking p110δ activity. Therefore, bone marrow-derived macrophages from the transgenic p110δ knock-in (which is a "kinase-death" inactivating mutation) were used in the adsorption assay. figure 1 D shows that the adsorption of VVL15 to ...

Embodiment 2

[0071] Example 2: Efficacy Study

[0072] Subsequently, this combination of inhibitor and virus was used in two efficacy studies in different mouse models ( figure 2 B and 2C), one of which has been optimized as a reliable model of orthotopic metastasis, which reflects the possible clinical application of this treatment. These studies demonstrate that IC87114 enhances the antitumor efficacy of systemically delivered VVL15 in vivo, conferring reduced tumor burden and survival advantages. Group D mice (IC87114+VVL15, figure 2 B and 2C) Tumor size eventually began to increase and the mice died, but VVL15 is a thymidine kinase-deficient virus, far inferior to other available modified vaccinia viruses carrying immune-modulating transgenes.

[0073] figure 2 E illustrates ex vivo interferon gamma assays performed on splenocytes from BALB / c mice bearing CT26 tumors. This demonstrates that splenocytes from mice treated with the optimized regimen developed anti-tumor IFNγ resp...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention provides a composition comprising a phosphatidylinositol 3-kinase (PI3K) inhibitor and a modified virus for separate, subsequent or simultaneous use in the treatment of cancer, wherein the modified virus is for intravenous administration.

Description

technical field [0001] The present invention relates to improved methods of delivering modified viruses to patients, eg, in cancer treatment. Background technique [0002] Modified viruses are viruses that have been selected or engineered for enhanced targeting and killing of cancer cells. Modified viruses can include replication competent viruses, conditional replication competent viruses, replication defective viruses, and attenuated viruses. In addition, the modified virus can also provide the immunostimulatory signals necessary to increase the host's own anti-cancer response. [0003] Despite advances in minimally invasive surgery, hyperfractionated radiation therapy, and new combinations of chemotherapeutic agents, survival rates for patients with many solid tumor types remain unchanged. Modified viruses are attractive therapies for the treatment of cancers that are resistant to conventional therapies. [0004] Modified viruses are excellent platforms for the deliver...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/06A61K35/76A61P35/00A61K31/52
CPCA61K45/06A61K31/52A61K35/76A61P35/00Y02A50/30A61K2300/00A61K9/0019
Inventor 王尧河马克·弗格森尼古拉斯·R·勒莫因
Owner QUEEN MARY UNIV OF LONDON
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com